Memory and Its Disorders

10/29/2019

Jason Brandt, Ph.D. Professor of Psychiatry & Behavioral Sciences Professor of Neurology The Johns Hopkins University School of Medicine

Memory

• “Without memory, there is no identity, and without identity we are cast adrift into a sea of chance, without compass, map or destination.” » Lord Jonathan Sacks, Former Chief Rabbi of the U.K.

Memory

• “Without memory, our existence would be barren and opaque, like a prison cell into which no light penetrates; like a tomb which rejects the living. If anything can, it is memory that will save humanity. For me, hope without memory is like memory without hope…” »Elie Wiesel

Outline

• Memory that is abnormally bad • Memory that is abnormally good • Malleability of memory • Memory for trauma • Common myths about memory

Outline

• Memory that is abnormally bad • Memory that is abnormally good • Malleability of memory • Memory for trauma • Common myths about memory

Theodore Ribot 1839-1916

Amnesia • Severe impairment in the ability to: – create new, permanent memories • anterograde amnesia – retrieve old, previously acquired information • retrograde amnesia • Due to brain dysfunction

Amnesia • Can be seen in isolation – the amnestic syndrome • Can also be seen in combination with other cognitive impairments – dementia, delirium, etc. • Distinguish from “pseudoamnesia” – psychogenic, conversion disorder, dissociative disorder

Some Causes of Amnesia • Traumatic brain injury • Cerebral anoxia (lack of oxygen) • Infections of the brain (encephalitis) •Strokes • Severe nutritional deficiencies • Degenerative brain disease – Alzheimer’s disease – Other dementias

Characteristics of the Amnestic Syndrome

• Anterograde amnesia • Retrograde amnesia • Normal immediate memory • Normal intelligence – No dementia, mental retardation • + Confabulation

The Experience of Amnesia

• “Right now, I’m wondering. Have I done or said anything amiss? You see, at this moment, everything looks clear to me, but what happened just before? That’s what worries me. It’s like waking from a dream.” » Henry Molaison (“H.M.”)

Case Examples of Amnesic Patients

•Patient R.J. – Viral (probably H. simplex) encephalitis •Patient O.N. – Alcoholic Korsakoff syndrome • Patient S.C. – Anterior communicating artery aneurysm

Patient R.J. • Age 55; College graduate • Viral encephalitis (probably H. simplex) • Bilateral mesial temporal lobe lesions on MRI scan • MMSE=25 • WAIS-R: VIQ=122, PIQ=95, FSIQ=111 • Verbal Fluency: normal • Wisconsin Card Sorting Test: normal • WMS-R: A/C=111, Gen’l Mem.=89, Delayed=54 • Severely impaired on all other anterograde memory tests • Retrograde amnesia limited to few years immediately prior to illness

Patient R.J.

Atrophy of Hippocampal Formation in Mild AD (Jack et al., 1997)

75 y.o. normal woman 73 y.o. woman with AD (CDR=1)

Tail

Body

Head

Patient O.N. • 82 year-old man • Highly accomplished attorney • Formerly, severe alcohol abuser • MMSE=27 • Full-Scale I.Q. = 132 on WAIS-R (99th percentile) • Wechsler Memory Scale – Revised – Attention Concentration Index = 131 (98th percentile) – General Memory Index = 81 (10th percentile) – Delayed Memory Index = 56 (< 1st percentile) • Severely impaired on all other anterograde memory tests • Extensive, temporally-graded retrograde amnesia

Patient O.N.

Verbal Paired-Associates

METAL -- IRON BABY -- CRIES CABBAGE -- PEN SCHOOL -- GROCERY FRUIT -- APPLE CRUSH -- DARK ROSE -- FLOWER OBEY -- INCH

Patient O.N. Verbal Paired-Associate Learning

Patient O.N.

Copy

Recall at 5 min.

Patient O.N.

Sketch of his former home from memory

Wernicke-Korsakoff Syndrome • Named after Carl Wernicke (German neurologist) and S.S. Korsakoff (Russian psychiatrist), who described two related syndromes in the 1880’s

Wernicke-Korsakoff Syndrome

• Acute onset of confusional state and ophthalmoplegia (Wernicke encephalopathy) • If patient survives, he is left with a severe and relatively permanent amnestic syndrome (Korsakoff syndrome) – Severe anterograde amnesia – Graded retrograde amnesia – Tendency to confabulate – Normal intellect • Caused by Vitamin B1 (thiamine) deficiency • Typically seen in severe, chronic alcoholics – But also in patients with malabsorption syndromes, stomach cancer, anorexia nervosa, etc. • Hemorrhagic lesions in thalamus (esp. dorsomedial nucleus) and mammillary bodies of hypothalamus

Patient S.C.

• Woman in early 60’s • Ph.D. in literature • Highly accomplished college professor • Acute onset of amnesia after surgery

Patient S.C.

INTELLECT LEARNING & MEMORY

Patient S.C. Verbal Paired-Associate Learning

Semantically Semantically Related Unrelated

Patient S.C. Working Memory and Procedural Learning

“What do I do?”

Varieties of Amnesia • Mesial Temporal/Limbic – Pathology in hippocampal formation – Severe anterograde amnesia – Limited retrograde amnesia – Seen post-encephalitis, anoxia, post ECT (time-limited) • Diencephalic – Pathology in dorsomedial thalamus and/or mammillary bodies – Severe anterograde amnesia – Can have extensive retrograde amnesia (esp. if cortex is involved) – Seen in Korsakoff syndrome, thalamic strokes, tumors, etc. • Frontal Lobe – Pathology in prefrontal cortex, anterior cingulate and/or basal forebrain – Forgetting to remember – Poor source memory – Impaired working memory

Memory for the Past • As opposed to capacity for new learning • Physicians (and others) often refer to this as “long term memory” • Impairment of acute or subacute onset is called “retrograde amnesia” • Rarely assessed systematically in routing clinical practice

Assessing Memory for the Past

• Recent past and remote past • Autobiographical events or public events • Challenges: – How to verify initial learning and storage – How to equate items for difficulty • Across time periods • Across individuals

Outline

• Memory that is abnormally bad • Memory that is abnormally good • Malleability of memory • Memory for trauma • Common myths about memory

3 Types of Extraordinary Memory

• Natural Mnemonists – Luria’s Sheveshevskii (“S”) (1968) • Intellectually gifted; very pronounced synesthesia • Learned a nonsensical mathematical formula of 50 elements in 7 minutes – Recalled it 15 years later • Little capacity for abstraction or metaphorical thinking; occupationally disabled – Hunt’s Professor Aitken (1977) • Brilliant mathematician and accomplished violinist • Learned list of 25 high-imagery words in 1.67 min. – Retained 25 at 1 week, 22 at 3 months, 24 at 15 months, 25 at 27 years • For fun, he learned pi to 1,000 decimal places • Used no specific mnemonics, except for chunking and pacing/rhythm

3 Types of Extraordinary Memory • Memory Champions – People who work on improving their memories, often for competitions – Chase & Ericsson’s S.F. (1982) • Undergraduate at Carnegie-Mellon University • Trained on digit span for hundreds of hours over two years – Resulted in digit span of 82 – Transferred to recall of visually-presented matrix of 25 or 50 digits – No transfer to non-numeric tasks; letter span = 6 • Encoded chunks of 3-4 digits into foot-race times (he was an amateur runner), ages or dates • Other undergraduates of Chase & Ericsson were less successful – Brain imaging studies find no systematic neuroanatomic differences between memory champions and others (Maguire et al. 2003)

Highly Superior Autobiographical Memory (HSAM)

• Originally described by Parker, Cahill & McGaugh (2006) – Called “hyperthymesia” • from the Greek thymesis, meaning remembering • Extraordinary ability to describe, in detail, events from their personal past (including days and dates) • Do not engage in extensive practice or rehearsal, or employ specific mnemonic strategies – Distinguishes them from mnemonists (such as Luria’s patient S) and memory champions (such as contestants at annual Memory Olympics)

Highly Superior Autobiographical Memory (HSAM) • Previously described cases… – are few in number • largest series of confirmed cases is 11 (James McGaugh and colleagues at U.C. Irvine) – including actress Marilu Henner – do not have autism and are not “savants” – do not have synesthesia – often have obsessional traits – are not immune from memory distortions – perform in the average range on clinical tests and laboratory tasks involving new learning and memory

Highly Superior Autobiographical Memory (HSAM)

Subject M.M

• 63 year-old, right-handed, Caucasian man • Reported an uncanny ability to remember historical facts and dates, sports statistics, and popular culture trivia, as well as events from his own life • Was dubbed “The Amazing Memory Man” by a local newspaper when he came to public attention in 1980’s – Pointed out an erroneous date on Baltimore’s Washington Monument • Special interests in – Professional athletics, Olympic games – British history, American history • Remembers the dates of every one of the many concerts and sporting event he has attended – Recalls performers, players, scores, etc. • Unlike other people with HSAM, does not recall virtually every day of adult life in vivid detail

Some Examples of M.M.’s Extraordinary Memory • Historical Significance of Random Dates: – May 18th: “That was the birthdate of Pope John Paul II, in 1920, and Baltimore Oriole Brooks Robinson, in Arkansas, in 1937. It was also the date that Mount Saint Helens volcano erupted in 1980.” –July 21st: became tearful,“That’s the date my mom died in 1987. Also, the first major battle of the Civil War, the Battle of Bull Run, was on that date in 1861. Also, Cat Stevens, who wrote my favorite song, ‘Morning Has Broken,’ was born on July 21, 1948.”

Some Examples of M.M.’s Extraordinary Memory • Historical Significance of Random Dates: – December 14th: “That’s a very sad day. The Sandy Hook School shooting happened then, in 2012.” – May 25th: “In 1935, Olympian Jesse Owen first became famous. Running in a collegiate track meet, he set 3 world records and tied a 4th in less than an hour. And, on that very day, Babe Ruth hit the last 3 home runs of his career. He was playing for the Boston Braves at that time, and they were in Pittsburgh playing the Pirates. And his team still lost, 11-7. Can you believe that?!”

Date Significance

• MM was given 30 random dates (e.g., Feb. 20, Nov. 12) and asked to describe something important that happened on each – Dates of clear historical significance (e.g., July 4, Sept. 11) excluded • Successful for 27 out of 30 – Accuracy confirmed by Wikipedia and other internet resources – Often supplemented with personal memories on those dates – For two dates, only personnel recollections – Half-correct for November 26 • Informal survey of Johns Hopkins Division of Medical Psychology personnel yielded scores of zero for everyone

Probability of Recall of U.S. Presidents

• (A) College students; data collected in different years

• (B) Adults of different generations; data collected in 2014

(Roediger & Abel, 2015)

Probability of Recall of U.S. Presidents by Subject M.M.

• MM was 100% correct in identifying these people • Added amusing trivia about many of them • Knew dates of birth and death for many of them

Semantic Fact Retrieval • Provide one-word answers to general information (world knowledge) questions • 75 items sampled from the Nelson & Narens (1980) corpus of 300 items – Re-normed on college students by Tauber et al. (2013) •Easy – What is the name of a giant ocean wave caused by an earthquake? (Tsunami) – In which sport does a rider on horseback hit a ball with his mallet? (Polo) – Of which country is Buenos Aires the capital? (Argentina) • Medium – What is the name of the lightest wood known? (Balsa) – What kind of poison did Socrates take at his execution? (Hemlock) – What is the last name of the author of the James Bond novels? (Fleming) •Hard – What was the name of the goldfish in the story of Pinocchio? (Cleo) – What is John Kenneth Galbraith’s profession? (Economist) – What is the name of the town through which Lady Godiva supposedly made her famous ride? (Coventry)

Varieties of Memory Assessed in Subject M.M.

Rating Test Variables

Wechsler Memory Scale, Rey-Osterrieth NEW LEARNING Episodic -- Complex Figure recall

AMI Personal Semantics, Personal Facts/Semantics AUTO- ↑↑↑ Residences BIOGRAPHIC Incidents/Episodes ↑↑↑ AMI Autobiographical Incidents

PRIOR World Knowledge/Semantics Date Significance, Fact Retrieval MEMORIES ↑↑↑

GENERIC Famous People ↑↑↑ Presidents, Celebrity Faces

Public Events/Episodes ↑↑↑ Date Significance, Oscar Test

Brain Structures Often Implicated in HSAM

Forceps major

Structural Imaging

Neuroradiologist Report:

Group •No gross structural Average abnormality •Multiple punctate white matter FLAIR hyperintense lesions in the periventricular and cortical regions, likely reflecting small vessel ischemic change M.M.

Structural Imaging

Controls M.M. Controls

Structural Imaging

• Left temporal “inclusion” – Band of white matter encircling a ring- like section of grey matter – In the perirhinal and entorhinal cortex • Left collateral sulcus – Defines the anterior boundary of the perirhinal cortex – Extremely deep (16.25 mm) • Seen in ~2% of cases

Functional Imaging

• Two resting-state fMRI scans • MM compared to mean of 5 age-matched men • Connectivity analysis performed using left hippocampus “seed” • LIBERAL definition of cluster – Voxelwise p=.05 – Cluster defined as > 20 contiguous voxels

Functional Imaging

• Increased connectivity in M.M. – L inferior prefrontal cortex (BA47) – L inferior frontal pars opercularis (BA44) – L premotor cortex (BA6) – L dorsolateral prefrontal cortex (BA46) – L retrosplenial cingulate cortex (BA29) – R dorsolateral prefrontal cortex (BA46)

Functional Imaging

• Decreased connectivity in M.M. – R posterior entorhinal cortex (BA28) – R perirhinal cortex (BA35) – L perirhinal cortex (BA35)

How Might We Understand MM’s Extraordinary Memory?

• Frontotemporal “hyperconnectivity”? – Increased synchrony between the hippocampal system and prefrontal cortex (PFC). • Regions of the PFC appear essential for maintaining an “episodic retrieval mode” – Phillippi et al. (2015); Spreng & Grady (2010) – Other HSAM patients have described “uncontrollable remembering” and “thinking about the past all the time” » Perhaps they can’t “turn off” or inhibit the episodic retrieval mode » Related to obsessionality? • Parts of the PFC appear essential for “memory integration”; inter-connecting related memories – Schlicting et al. (2015a,b) – Perhaps this underlies MM’s tendency to form connections between unrelated, but coincidental, personal and public events

How Might We Understand MM’s Extraordinary Memory?

• Increased cross-talk between semantic and episodic memory systems? – MM has a strong tendency to • Infuse recollections of personal experiences with their historical or cultural context • Insert his own life experiences into answers to general information questions – The boundaries between facts and episodes and between the personally experienced and the historical appear especially fluid in MM – Semantic knowledge that is associated with autobiographical experiences has special status in LTM • Westmacott & Moscovitch (2003)

Outline

• Memory that is abnormally bad • Memory that is abnormally good • Malleability of memory • Memory for trauma • Common myths about memory

Memories are NOT Forever • Memories can be changed by events that occur AFTER the memory is recorded • Misinformation can supplant original information • Laboratory and “real-world” research by Elizabeth Loftus, Ph.D.

Loftus & Palmer (1974)

• Subjects watched a videotape of a car accident • One of two questions was asked: – “How fast was the red car going when it hit the green car?” or – “How fast was the red car going when it smashed into the green car?” • 7 mph faster in the second condition

One Week Later

Research on Memory Distortion

“Did another car pass the red Datun while it was at the stop/yield sign?”

Loftus • Implied facts – “Did you see a broken headlight?” versus – “Did you see the broken headlight?” • Those asked the second condition will have a significantly altered memory. – All due to a single word! • Good trial attorneys know this and use it when questioning witnesses.

Implanted Memories of Events that Never Happened

• Overnight hospitalization: 20% agreed • Accident at a wedding: 25% agreed • Serious animal attack: 28% agreed • Rescued by a lifeguard: 37% agreed

Implanted Memories of Seeing Bugs Bunny Character at Disneyland

• Shook his hand… 62% • Hugged him… 46% • Touched his ear… 23% • Touched his tail… 23% • Heard him say “what’s up doc?”… 23% • COULD NOT HAVE HAPPENED! – Buggs Bunny is a Warner Brothers, not a Disney, cartoon character

Pros and Cons of Memory Malleability

•Pros • Cons – Allows one to – What is TRUTH? “reframe” and “re- – Wrecks havoc with remember” painful the legal system experiences • Limits the reliability – A major component of eyewitness and of psychotherapy is other testimony “rescripting” the past

Outline

• Memory that is abnormally bad • Memory that is abnormally good • Malleability of memory • Memory for trauma • Common myths about memory

Is Trauma Special When it Comes to Memory?

• Some experts argue that combat, rape, and other horrible experiences are never forgotten – We remember them too well • Others argue that the “psyche” (mind) can protect itself by banishing these experiences from awareness – We repress (don’t remember) them

Is Trauma Special When it Comes to Memory? • Although some “traumatologists” believe that the principles of memory do not apply to very emotionally charged events, there is no scientific support for this. • The rules do apply! – The more often something happens, the more likely it is to be remembered. – The more emotionally arousing the event, the more likely it will be remembered. – The longer ago the event happened, the less likely it is to be remembered accurately.

Is Trauma Special When it Comes to Memory?

• Memories of traumatic events – Are not “repressed.” • In fact, they are more likely to be remembered because of their emotional salience. – Are not “frozen” or immutable. • “Flashbacks” of PTSD, for example, might seem like re-experiencing of events, but this is illusory – Are not stored as “body memories.” – Are not more accurate if they are more vivid.

False Memory Syndrome • Memories of trauma (often of childhood sexual abuse) that were “repressed” and then “recovered” during psychotherapy • Many of these recovered memories were later found to be factually impossible – e.g., the perpetrator was overseas or in prison at the time • In many cases, these memories were encouraged by therapists because they fit a theory or narrative in which they believed • Destroyed many families

Memory-Dampening Drugs

• Medications currently exist that can – with a single dose – permanently eliminate the emotionally-painful component of a traumatic memory. • “If you were the victim of a serious crime, would you want such a drug?” – 80% said “no” • “If you saw a military buddy blown up by an IED overseas, would you want such a drug?” – 80% said “no”

Outline

• Memory that is abnormally bad • Memory that is abnormally good • Malleability of memory • Memory for trauma • Common myths about memory

Myths About Human Memory

• Everything we’ve ever experienced is stored permanently in memory. • Amnesics lose their identities. • A blow to the head can produce amnesia and another blow can restore memory. • Memories of emotionally traumatic events are typically repressed. • Traumatic memories can be recovered accurately with hypnosis or psychotherapy.

Common Incorrect Beliefs About Memory Simons & Chabris (2011)

• Telephone survey of 1,838 people in U.S. in June 2009 • Sample was reduced to 1,500 to produce final sample representative of population in sex, age, race, and region of country • Asked extent of agreement with 6 statements about memory • Compared results to those of 16 memory experts (professors with more than 10 years experience in memory research)

Common Incorrect Beliefs About Memory Simons & Chabris (2011)

Public Expert Item Agreement Agreement People suffering from amnesia typically cannot recall their own name 83% 0% or identity The testimony of one confident eyewitness should be enough to 37% 0% convict a defendant of a crime Human memory works like a video camera, accurately recording the events we see and hear so that we 63% 0% can review and inspect them later

Common Incorrect Beliefs About Memory Simons & Chabris (2011)

Public Expert Item Agreement Agreement Hypnosis is useful in helping witnesses accurately recall details of 55% 0% a crime People generally notice when something unexpected enters their field of view, even when they’re 78% 19% paying attention to something else

Once you have experienced an event and formed a memory of it, that 48% 0% memory does not change

Trauma-Informed Care

• Is simply good, solid, clinical care, blending sensitivity and compassion with scientific evidence. • Avoid being snared in the trap of “traumatologists” and well-meaning but misguided therapists whose personal beliefs in outdated, poorly- supported theory lead them astray.

Thank You!